Numerical analysis of the size-based, shear-induced separation of circulating tumour cells from white blood cells in liquid biopsies

Circulating tumour cells (CTCs) are promising biomarkers for early cancer detection, yet their extreme rarity in blood necessitates efficient separation from white blood cells (WBCs) in lysed liquid biopsies. Inertial microfluidics offers a high-throughput, label-free approach to this challenge by leveraging size-dependent lateral migration. However, experimental observations reveal that WBCs migrate more rapidly than predicted, reducing separation performance. Using 3D lattice-Boltzmann-immersed-boundary-finite-element simulations, we characterized the migration dynamics of CTCs and WBCs in a straight microchannel. Our results reveal that the presence of a CTC enhances WBC cross-streamline migration, providing a mechanistic explanation for WBC contamination in CTC-enriched outlets. The numerical model capturing heterochiral orbital dynamics was validated experimentally, confirming the role of intercellular hydrodynamic interactions. These findings underscore the critical role of intercellular interactions in inertial microfluidic systems and provide guidance for optimizing suspension concentration and channel geometry to improve purity in rare cell isolation.